CCG Chemical Libraries

CCG Chemical Library available in 384-well formats, all DMSO stocks at 2mM, 5mM and 10mM (except where noted)

Group 1: NPEs

33,000 Natural Product Extracts are derived from a collection of sediments, cyanobacteria and sponges from all over the world (Papua New Guinea, Costa Rica, Panama, Lake Erie, Lake Huron, Nepal, Middle East, Peru, Brazil, and Antarctica). The sediments collected are full of bacterial cells and spores which when placed on petri dishes under carefully monitored conditions will allow the cells to grow. It takes two weeks to several months for the microbes to appear. Once a potentially promising organism is detected, it is streaked onto rich media plates in order to obtain a pure culture. The subsequent inoculated liquid cultures grow the newly discovered bacteria to suitable cell mass so that the new natural product molecules can be extracted and analyzed for biological activity in HTS screening. The extracts contain more than one compound, so when activity is found in an extract there is fractionation and isolation in order to characterize the natural product responsible for the activity. Once a hit is identified, active fractions are tested and then purified to obtain sufficient amounts for structural characterization, and transfer to the pure compound library. Then the bacteria used to prepare the samples are phylogenetically characterized using 16S rRNA gene sequence analysis, cell wall composition and fatty acid analysis, menaquinone characterization and genome sequence analysis followed by natural product gene cluster mining. The Sherman laboratory will continue to expand the number of pure culture strains by at least 500/year (currently ~5000). NPE library expansion will occur at an estimated rate of at least 1000/year.

Group 2: Custom Drug Libraries

UM Chemistry is a collection is currently 886 compounds obtained from UM chemists and medicinal chemists for testing with UM projects

CMLD is 2,456 compounds from Chemical Methodology Library Development (CMLD) Program, Boston University and University of Kansas for UM Projects.

NCI is a collection from National Cancer Institute with 3,227 compounds known to be active in oncology targets. 2270 compounds are available on 384-well plates

NCC is NIH Clinical Compound library with 445 compounds that have a history of use in human clinical trials

Pathways is a collection of 1037 compounds from several vendors that are known actives: autophagy, Wnt Pathway, epigenetics, protein kinase, protease, REDOX, cannabinoid. It also includes purified natural products.

Group 3: Commercial Drug-Like Molecules

MB24K is a library from Maybridge that has 23,552 samples of diverse compounds that were cherry-picked from the Maybridge library with oversight by pharmaceutical medicinal chemists.

ChemDiv 100K is a library of 100,000 compounds cherry-picked from ChemDiv with oversight by CCG medicinal chemists.

ChemDiv 20K is a library of 20,000 compounds cherry-picked from ChemDiv with oversight by CCG medicinal chemists.

LOPAC is Library of Pharmacologically Active Compounds from Sigma with 1280 samples

Prestwick is unique collection of 1280 small molecules, 100% approved drugs (FDA, EMA and other agencies) selected by a team of medicinal chemists and pharmacists for their high chemical and pharmacological diversity as well as for their known bioavailability and safety in humans.

Kinase includes the Enzo Kinase Inhibitor Library containing 80 known inhibitors of well-defined activity. It also includes additional 23 compounds known kinase inhibitors (purchased by CCG) and 217 compounds from the ChemBridge KINA set.MB 16K is 16,000 compound Maybridge HitFinder (retired 2016)

CB 10K and CB 3K are 13,028 compounds from ChemBridge (retired 2014).

Group 4: Chemical Fragments

A collection of 2668 fragments that includes the 1800 compounds from Asinex BioFragments subset. Fragment screening is an approach that aims to increase the chances of finding chemicals that can target protein-protein interactions or other novel and challenging drug targets by testing small chemical fragments that can bind to the target with low affinity. These fragments (MW 150-300) also have functional groups that permit facile chemical extension to engage additional surfaces on the protein target. With this approach, larger compounds with high affinity for the target can be built either by extension with novel building blocks or by linking of two low affinity fragments found by screening. Importantly, starting with simpler compounds reduces the overall chemical space that needs to be explored. This makes it feasible to do screens with a few thousand fragments rather than the 100’s of thousands drug-like compounds that are often screened from diversity libraries. The collection is maintained in several formats to facilitate many different methods of screening: NMR, differential scanning fluorimetry (DSF, ThermoFluor), label-free biomolecular interaction analysis. This collection also has powder samples available at the CCG following hit selection from DMSO samples.